There is a rapidly emerging literature showing not only interactive feedback between the neural, endocrine and immune systems, but also that the cells of the immune system produce and have receptors for opioids. A limited number of published studies have shown immunosuppressive effects of opioids in vitro. As chronic drug abusers are at increased risk of acquiring infectious diseases, including HIV, it is of interest to explore the hypothesis that drug usage may predispose to infection by immunosuppression. It is proposed to carry out a systematic investigation of the effects of opioids on parameters of immune responsiveness and resistance to infection in rodents. As our preliminary studies indicate that opioids are immunosuppressive, it is further proposed to assess which cells of the immune system are targets for modification by opioids; to determine with selective ligands which of the opioid receptor types is/are involved in alteration in immune system function, and to determine if there is an interaction among the various opioid receptor systems in terms of alteration in immune function. Such interactions could be additive, greater than additive, or antagonistic. Both in vivo and in vitro assays of immune function will be used, as well as in vivo administration of drugs and in vitro assay of immune responses. In vitro assays will permit extensive dose response and drug interaction studies as well as identification of target cells, identification of mechanisms of immunosuppression, and of receptor types. In vivo assays will allow evaluation of the significance of observations made in vitro, which may be particularly important in light of the feedback interactions between the immune and other homeostatic systems. These studies are of significance in that they can provide a scientific basis for understanding how opioids adversely affect immune competence and susceptibility to infectious diseases. Such studies are especially timely in view of the connection between IV drug abuse and AIDS.